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Evaluation of potential RKIP and SDHB biomarkers in gastrointestinal stromal tumors (GISTs)

Grant number: 17/05843-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2017
Effective date (End): June 30, 2018
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Rui Manuel Vieira Reis
Grantee:Richard Lucas Konichi Dias
Home Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

The gastrointestinal stromal tumors (GISTs) are neoplasms of stromal origin most common in the gastrointestinal tract. Mutations at the oncogenes KIT/PDGFRA are present in about 85% of this neoplasms. They induce constitutive activation of the proliferation pathways and cell survival and, because of it, they are currently targets of the molecular treatment with the drug Imatinibe. Our group has previously identified a lost of expression of a metastasis suppressor molecule, the RKIP, in about 17% of the GISTs. We observed a tendency of the cases with expression lost of the RKIP, to have a worst global survival, however, the small number of samples made it impossible to associate with the prognosis with statistic significance. More recently it has been demonstrated the central importance of the loss of SDHB expression in wild KIT/PDGRFA. Therapeutically the cases with SDHB alteration did not answer to Imatinibe. In this sense, a better understanding of new mechanisms in the pathogenesis of GISTs will facilitate the identification of new and effective target therapies. This work purpose is to avaliate the expression of two potential biomarkers, RKIP and SDHB, in a serie of 200 cases of GIST and correlate with clinical pathological and molecular data (mutation of KIT, PDGFRA e BRAF) of patients. The immunohistochemistry will be performed according to the streptovidin-peroxidase method and the analysis will be performed using the following score: negative ( absence of marking (-) or with weak marking (+) and positive (moderate marking (++) or strong (+++)). The clinical data, molecular and immunohistochemistry of each patient will be collected through a review of the medical records and the data collection record previously standardized. (AU)